piperidin-4-ylmethyl acetate | 500786-59-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: piperidin-4-ylmethyl acetate
• CAS: 500786-59-4
• 化学式: C₈H₁₅NO₂
• mdl: MFCD13183949
• 分子量: 157.213
• InChiKey: KQGBGOUNTHYCMQ-UHFFFAOYSA-N

物化性质

• 沸点：
  213.1±13.0 °C(Predicted)
• 密度：
  0.982±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  11
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.875
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-((2-fluoroethyl)sulfonyl)-4-methylbenzene 、 piperidin-4-ylmethyl acetate 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 以73%的产率得到N-[18F]fluoroethylpiperidin-4ylmethyl acetate
  参考文献：
  名称：

  N-[¹⁸F]Fluoroethylpiperidin-4ylmethyl Acetate, a Novel Lipophilic Acetylcholine Analogue for PET Measurement of Brain Acetylcholinesterase Activity

  摘要：

  The reduction of acetylcholinesterase (AChE) activity in the brain has been measured in dementia disorders such as Alzheimer's disease and dementia with Lewy bodies using C-11-labeled acetylcholine analogues, N-[C-11]methylpiperidin-4-yl acetate and propionate, and positron emission tomography (PET). Our aim was to develop an F-18-labeled acetylcholine analogue useful for brain AChE mapping with PET, since F-18, with a longer half-life, has advantages over C-11. In a preliminary study, a series of N-[C-14]ethylpiperidin-3-yl or -4yl-methanol esters (acetyl and propionyl esters) were newly designed and evaluated in vitro regarding the reactivity with and specificity to AChE using purified human enzymes, leading to a novel F-18-labeled acetylcholine analogue, N-[F-18]fluoroethylpiperidin-4-ylmethyl acetate. In rat experiments, the F-18-labeled candidate showed desirable properties for PET AChE measurement: high brain uptake of the authentic ester, high AChE specificity, a moderate hydrolysis rate, and low membrane permeability (metabolic trapping) of the metabolite.

  DOI：

  10.1021/jm049100w
• 作为产物：
  描述：

  N-tert-butoxycarbonylpiperidin-4-ylmethyl acetate 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 1.0h， 生成 piperidin-4-ylmethyl acetate
  参考文献：
  名称：

  N-[¹⁸F]Fluoroethylpiperidin-4ylmethyl Acetate, a Novel Lipophilic Acetylcholine Analogue for PET Measurement of Brain Acetylcholinesterase Activity

  摘要：

  The reduction of acetylcholinesterase (AChE) activity in the brain has been measured in dementia disorders such as Alzheimer's disease and dementia with Lewy bodies using C-11-labeled acetylcholine analogues, N-[C-11]methylpiperidin-4-yl acetate and propionate, and positron emission tomography (PET). Our aim was to develop an F-18-labeled acetylcholine analogue useful for brain AChE mapping with PET, since F-18, with a longer half-life, has advantages over C-11. In a preliminary study, a series of N-[C-14]ethylpiperidin-3-yl or -4yl-methanol esters (acetyl and propionyl esters) were newly designed and evaluated in vitro regarding the reactivity with and specificity to AChE using purified human enzymes, leading to a novel F-18-labeled acetylcholine analogue, N-[F-18]fluoroethylpiperidin-4-ylmethyl acetate. In rat experiments, the F-18-labeled candidate showed desirable properties for PET AChE measurement: high brain uptake of the authentic ester, high AChE specificity, a moderate hydrolysis rate, and low membrane permeability (metabolic trapping) of the metabolite.

  DOI：

  10.1021/jm049100w

文献信息

• [EN] SUBSTITUTED 1,5-NAPHTHYRIDINES OR QUINOLINES AS ALK5 INHIBITORS<br/>[FR] 1,5-NAPHTYRIDINES OU QUINOLÉINES SUBSTITUÉES EN TANT QU'INHIBITEURS D'ALK5
  申请人：THERAVANCE BIOPHARMA R&D IP LLC

  公开号：WO2021102468A1

  公开（公告）日：2021-05-27

  The present disclosure provides inhibitors of activin receptor-like kinase 5 (ALK5). Also disclosed are methods to modulate the activity of ALK5 and methods of treatment of disorders mediated by ALK5.

  本公开提供了激活素受体样激酶5（ALK5）的抑制剂。还公开了调节ALK5活性的方法和通过ALK5介导的疾病的治疗方法。
• [EN] PIPERAZINYL NORBENZOMORPHAN COMPOUNDS AND METHODS FOR USING THE SAME<br/>[FR] COMPOSÉS DE PIPÉRAZINYL NORBENZOMORPHANE ET PROCÉDÉS D'UTILISATION DE CEUX-CI
  申请人：UNIV TEXAS

  公开号：WO2017070229A1

  公开（公告）日：2017-04-27

  Disclosed herein, inter alia, are piperazinyl norbenzom orphan compounds and uses thereof, including, for example, methods for treating a CNS disease, treating traumatic brain injury, improving cognition, or diagnosing and treating cancer.

  本公开的内容包括哌嗪基苯并孤儿化合物及其用途，例如用于治疗中枢神经系统疾病、治疗创伤性脑损伤、改善认知功能，或诊断和治疗癌症的方法。
• A Simple, General, and Highly Chemoselective Acetylation of Alcohols Using Ethyl Acetate as the Acetyl Donor Catalyzed by a Tetranuclear Zinc Cluster
  作者：Takashi Ohshima、Kazushi Mashima、Takanori Iwasaki、Yusuke Maegawa、Yukiko Hayashi

  DOI：10.1055/s-0029-1217335

  日期：——

  presence of a Zn-cluster catalyst, alcohols are efficiently converted to the corresponding acetate just by refluxing in EtOAc. The mild reaction conditions enabled the reactions of various functionalized alcohols to proceed in good to excellent yield. Moreover, even when a large excess of the acetyl donor is used, the hydroxyl groups are selectively acetylated in the presence of highly nucleophilic aliphatic

  在 Zn 簇催化剂的存在下，仅通过在 EtOAc 中回流，醇就可以有效地转化为相应的乙酸盐。温和的反应条件使各种官能化醇的反应能够以良好的收率进行。此外，即使使用大量过量的乙酰基供体，羟基在高度亲核脂肪族氨基的存在下也会被选择性乙酰化，接近酶系统的化学选择性。
• AMINOTHIAZOLES AND THEIR USES
  申请人：Bushell Simon

  公开号：US20140315790A1

  公开（公告）日：2014-10-23

  The present application describes organic compounds that are useful for the treatment, prevention and/or amelioration of diseases.

  本申请描述了对治疗、预防和/或改善疾病有用的有机化合物。
• [EN] TRYPSIN AND THROMBIN INHIBITORS<br/>[FR] INHIBITEURS DE TRYPSINE ET DE THROMBINE
  申请人：NOVARTIS AG

  公开号：WO1996029327A1

  公开（公告）日：1996-09-26

  (EN) The present invention provides a compound of general formula (I), in which Ar is a substituted or unsubstituted aryl or heterocyclic residue; Aa is an amino acid residue usually of L configuration and (a) is a residue of formula (IV) or formula (V), wherein X is hydrogen or a C1-C5 alkyl group; Y is a) an SO3H, PO(OR14)2, OH, SH, NR15R16, or halogen group or is b) a residue -(CqH2q)-Q wherein Q is H, COR14, CO2R14, CONR15R16, SO3H, OR14, OCOR14, PO(OR14)2, NR15R16, SR14 or Hal wherein R14, R15 and R16 are hydrogen, C1-C5 alkyl, C5-C8 cycloalkyl or C7-C11 aralkyl or R15 and R16 together with the nitrogen atom to which they are bound form a 5 or 6 membered azacycloalkyl or oxazacycloalkyl, q is 0 or an integer from 1 to 8 and the residue CqH2q may be optionally substituted by OH or interrupted by oxygen, sulfur, oxycarbonyl O.CO, carbonyloxy CO.O, aminocarbonyl NHCO, sulfonamido, NHSO2 or carboxamido CONH; or is c) a residue (CwH2w+1-y-z)FyOHz in which w is an integer from 1 to 8, y is an integer from 1 to 17 and z is 0 or 1, or X and Y together are = O, Z is a direct bond, oxygen or nitrogen optionally substituted by X or Y, m = 2 to 4, n = 2 to 4 and m + n = 4 to 6, j = 0 to 2, k = 0 to 2 and j + k = 2 or 3, wherein X has its previous significance and Y is a residue (CqH2q)-Q, wherein q and Q have their previous significance, and salts thereof, provided that when As is arginine, X and Y are not alkyl and when Q is COR14, q is an integer from 1 to 8.(FR) La présente invention concerne un composé de la formule générale (I). Dans cette formule, Ar est un reste aryle ou hétérocyclique, substitué ou non; Aa est un reste d'acide aminé ayant généralement la configuration L et (a) est un reste ayant la formule (IV) ou (V). Dans ces formules, X est un hydrogène ou un groupe alkyle C1-C5, Y est a) un SO3H, PO(OR14)2, OH, SH, NR15R16 ou un groupe halogène, ou b) un reste -(CqH2q)-Q où Q est H, COR14, CO2R14, CONR15R16, SO3H, OR14, OCOR14, PO(OR14)2, NR15R16, SR14 ou Hal où R14, R15 et R16 représentent hydrogène, alkyle C1-C5, cycloalkyle C5-C8 ou aralkyle C7-C11 ou R15 et R16 forment ensemble avec l'atome d'azote auquel ils sont fixés un azacycloalkyle ou un oxazacycloalkyle à 5 - 6 éléments, q est égal à 0 ou à un nombre entier compris entre 1 et 8 et le reste CqH2q peut être, à titre facultatif, substitué par un OH ou interrrompu par un oxygène, un soufre, un oxycarbonyle O.CO, un carbonyloxy CO.O, un aminocarbonyle NHCO, un sulfonamido NHSO2 ou un carboxamido CONH; ou c), un reste (CwH2w+1-y-z)FyOHz dans lequel w est un nombre entier entre 1 et 8, y est un nombre entier entre 1 et 17 et z est égal à 0 ou 1, ou X et Y ensemble = 0, Z est une liaison directe, un oxygène ou un azote substitué éventuellement par X ou Y, m = 2 à 4, et m + n = 4 à 6, j = 0 à 2, k = 0 à 2 et j + k = 2 ou 3, où X a la signification précédente et Y représente un reste (CqH2q)-Q où q et Q ont la signification précédente. L'invention concerne également les sels de ces composés, à condition que, quand Aa représente l'arginine, X et Y ne représentent pas alkyle et quand Q représente COR14, q représente un nombre entier entre 1 et 8.

  本发明提供了一种通式（I）的化合物，其中Ar是取代或未取代的芳基或杂环残基; Aa通常是L构型的氨基酸残基，而（a）是式（IV）或式（V）的残基，其中X是氢或C1-C5烷基基团; Y是a）SO3H、PO（OR14）2、OH、SH、NR15R16或卤素基团，或者b）残基-(CqH2q)-Q，其中Q是H、COR14、CO2R14、CONR15R16、SO3H、OR14、OCOR14、PO（OR14）2、NR15R16、SR14或Hal，其中R14、R15和R16是氢、C1-C5烷基、C5-C8环烷基或C7-C11芳基烷基，或者R15和R16与它们所连接的氮原子形成5或6元杂环烷基或氧杂环烷基，q是0或1-8的整数，而残基CqH2q可以选择性地被OH取代或被氧、硫、氧羰基O.CO、羰氧基CO.O、氨基羰基NHCO、磺酰胺基NHSO2或羧酰胺基CONH打断；或者c）残基（CwH2w+1-y-z）FyOHz，其中w是1-8的整数，y是1-17的整数，z是0或1，或者X和Y一起是=O，Z是直接键，氧或氮，可选地被X或Y取代，m=2-4，n=2-4，m+n=4-6，j=0-2，k=0-2，j+k=2或3，其中X具有其先前的意义，而Y是残基（CqH2q）-Q，其中q和Q具有其先前的意义，以及其盐，但当Aa为精氨酸时，X和Y不是烷基，而当Q为COR14时，q是1-8的整数。